Seminar

Abstract

All diverse cell types in an organism essentially have an identical genome. Generation of
tissue specific cells is through an epigenomic process in which progressive alterations in
the chromatin state generates lineage committed cells from pluripotent embryonic stem
cells. Ultimately, establishment of terminally differentiated cells results in a stable
chromatin state.
Chromatin modification can be studied by chromatin immunoprecipitation (ChIP) that
identifies regions that are over-represented as transcriptionally active sequences.
In this talk we describe chromatin-state maps for pluripotent, cancer and lineagecommitted
cells using three-dimensional modelling of fibre conformation. The model
takes into account of the local structure of chromatin organised into euchromatin (open
chromatin), permissive for gene activation, and heterochromatin (closed chromatin),
transcriptionally silenced. Open chromatin is assumed to be modelled by a linker DNA
while the closed chromatin by means of a solenoid structure in which DNA winds onto
six nucleosome spools per turn with two left-handed superhelical turns around an histone
octamer. The model represents a single gyre of a solenoid by means of a torus knot that
winds around a torus once in the longitudinal direction and twelve in the meridian
direction. Closed and open chromatin is then connected by means of piecewise
polynomial transformations based on cubic Hermite spline functions. As reprogramming
process is associated both with pluripotency and the neoplastic process, our analyses
potentially identify cancer-related epigenetic abnormalities. Chromatin fibre
conformation are compared in terms of geometric quantities such as curvature and
torsion localization, and relative rates, in relation to filament compaction and packing
efficiency. This study provides information on relationships between geometry and the
transcriptional regulation in stem cells and cancer cells contributing to pluripotency and
self-renewal.

Video

The video for this talk should appear here if JavaScript is enabled.If it doesn't, something may have gone wrong with our embedded player.We'll get it fixed as soon as possible.